The aim of this program is to understand the principles, and mechanisms that govern communication between astrocytes and between astrocytes and neurons. Although neurons are the central players in cellular communication and information processing in the brain, recent discoveries of glial cell types, excitability and signalling properties have shown that glial cells may play an important role in long distance signalling in the brain. During embryonic development, release of specific humoral signals from glial cells are important for neuronal survival and development. In the adult, synaptic activity results in intracellular calcium signals in astrocytes closest to the synaptic fields. The cellular processes involved in this calcium based excitability resulting in long distance signalling in glia are not understood. Nor are the mechanisms that underlie calcium wave propagation in astrocytes. Methods have become available for obtaining relatively pure cultures of different types of astrocytes, as well as mixed neuronal and glial cultures. Methods are also available for light microscopic analysis of cells in slice preparations. Fluorescence microscopy with digital image processing will be used as the technique to monitor intracellular signaling in astrocytes in order to describe specific modes of cellular signalling. The intracellular calcium changed in response to activation of various neurotransmitter receptor systems on astrocytes isolated from different regions of brain will be investigated. The spatio-temporal characteristics of the receptor mediated intracellular calcium signals will be analyzed in detail with the view to understanding the underlying mechanisms and processes.